tbuckley/cabot-search huggingface dataset:
Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis
Authors: Oana Nicoară-Farcău, Guohong Han, Marika Rudler, Debora Angrisani, Alberto Monescillo, Ferran Torres, Georgina Casanovas, Jaime Bosch, Yong Lv, Philip D.J. Dunne, Peter C. Hayes, Dominique Thabut, Daiming Fan, Virginia Hernández-Gea, Juan C. García-Pagán
Journal: Hepatology (2023)

Background and Aims: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C&lt;14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues. Approach and Results: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival. We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32–0.60, p &lt;0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS. Conclusions: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients.
A subpopulation of lipogenic brown adipocytes drives thermogenic memory
Authors: Patrick Lundgren, Prateek V. Sharma, Lenka Dohnalová, Kyle Coleman, Giulia T. Uhr, Susanna Kircher, Lev Litichevskiy, Klaas Bahnsen, Hélène C. Descamps, Christina Demetriadou, Jacqueline Chan, Karthikeyani Chellappa, Timothy O. Cox, Yael Heyman, Sarshan R. Pather, Clarissa Shoffler, Christopher Petucci, Ophir Shalem, Arjun Raj, Joseph A. Baur, Nathaniel W. Snyder, Kathryn E. Wellen, Maayan Levy, Patrick Seale, Mingyao Li, Christoph A. Thaiss
Journal: Nature Metabolism (2023)
A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo
Authors: Eirini Giannakopoulou, Madeleine Lehander, Stina Virding Culleton, Weiwen Yang, Yingqian Li, Terhi Karpanen, Tetsuichi Yoshizato, Even H. Rustad, Morten Milek Nielsen, Ravi Chand Bollineni, Trung T. Tran, Marina Delic-Sarac, Thea Johanne Gjerdingen, Karolos Douvlataniotis, Maarja Laos, Muhammad Ali, Amy Hillen, Stefania Mazzi, Desmond Wai Loon Chin, Adi Mehta, Jeppe Sejerø Holm, Amalie Kai Bentzen, Marie Bill, Marieke Griffioen, Tobias Gedde-Dahl, Sören Lehmann, Sten Eirik W. Jacobsen, Petter S. Woll, Johanna Olweus
Journal: Nature Cancer (2023)

Abstract Acute myeloid leukemia (AML), the most frequent leukemia in adults, is driven by recurrent somatically acquired genetic lesions in a restricted number of genes. Treatment with tyrosine kinase inhibitors has demonstrated that targeting of prevalent FMS-related receptor tyrosine kinase 3 (FLT3) gain-of-function mutations can provide significant survival benefits for patients, although the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable. We identified a T cell receptor (TCR) reactive to the recurrent D835Y driver mutation in the FLT3 tyrosine kinase domain (TCR FLT3D/Y ). TCR FLT3D/Y -redirected T cells selectively eliminated primary human AML cells harboring the FLT3 D835Y mutation in vitro and in vivo. TCR FLT3D/Y cells rejected both CD34 + and CD34 − AML in mice engrafted with primary leukemia from patients, reaching minimal residual disease-negative levels, and eliminated primary CD34 + AML leukemia-propagating cells in vivo. Thus, T cells targeting a single shared mutation can provide efficient immunotherapy toward selective elimination of clonally involved primary AML cells in vivo.
Somatic evolution of marine transmissible leukemias in the common cockle, Cerastoderma edule
Authors: Alicia L. Bruzos, Martín Santamarina, Daniel García-Souto, Seila Díaz, Sara Rocha, Jorge Zamora, Yunah Lee, Alejandro Viña-Feás, Michael A. Quail, Iago Otero, Ana Pequeño-Valtierra, Javier Temes, Jorge Rodriguez-Castro, Leyre Aramburu, André Vidal-Capón, Antonio Villanueva, Damián Costas, Rosana Rodríguez, Tamara Prieto, Laura Tomás, Pilar Alvariño, Juana Alonso, Asunción Cao, David Iglesias, María J. Carballal, Ana M. Amaral, Pablo Balseiro, Ricardo Calado, Bouchra El Khalfi, Urtzi Izagirre, Xavier de Montaudouin, Nicolas G. Pade, Ian Probert, Fernando Ricardo, Pamela Ruiz, Maria Skazina, Katarzyna Smolarz, Juan J. Pasantes, Antonio Villalba, Zemin Ning, Young Seok Ju, David Posada, Jonas Demeulemeester, Adrian Baez-Ortega, Jose M. C. Tubio
Journal: Nature Cancer (2023)
Annals On Call - Low-Dose Colchicine and Incident Knee and Hip Replacements
Authors: Robert M. Centor, Tuhina Neogi
Journal: Annals of Internal Medicine (2023)

Web Exclusives3 October 2023Annals On Call - Low-Dose Colchicine and Incident Knee and Hip ReplacementsFREERobert M. Centor, MD, and Tuhina Neogi, MD, PhDRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author, and Tuhina Neogi, MD, PhDBoston University School of Medicine, Boston, Massachusetts (T.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A22-0019 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses the incidence of knee and hip replacements in patients receiving low-dose colchicine with Dr. Tuhina Neogi.Annals articles discussed include...Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements. Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial: https://www.acpjournals.org/doi/10.7326/M23-0289About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Robert M. Centor, MD; Tuhina Neogi, MD, PhDAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Boston University School of Medicine, Boston, Massachusetts (T.N.)Disclosures: All relevant financial relationships have been mitigated. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=A22-0019.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures.This article was published at Annals.org on 3 October 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAssociation of Low-Dose Colchicine With Incidence of Knee and Hip Replacements Michelle W.J. Heijman , Aernoud T.L. Fiolet , Arend Mosterd , Jan G.P. Tijssen , Bart J.F. van den Bemt , Astrid Schut , John W. Eikelboom , Peter L. Thompson , Cornelia H.M. van den Ende , Stefan M. Nidorf , Calin D. Popa , and Jan H. Cornel Metrics October 2023Volume 176, Issue 10 ePublished: 3 October 2023 Issue Published: October 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...
Diet and gut microbial associations in irritable bowel syndrome according to disease subtype
Authors: Yiqing Wang, Wenjie Ma, Raaj Mehta, Long H. Nguyen, Mingyang Song, David A. Drew, Francesco Asnicar, Curtis Huttenhower, Nicola Segata, Jonathan Wolf, Tim Spector, Sarah Berry, Kyle Staller, Andrew T. Chan
Journal: Gut Microbes (2023)

The role of diet and the gut microbiome in the etiopathogenesis of irritable bowel syndrome (IBS) is not fully understood. Therefore, we investigated the interplay between dietary risk factors and gut microbiota in IBS subtypes using a food frequency questionnaire and stool metagenome data from 969 participants aged 18–65 years in the ZOE PREDICT 1 study, an intervention study designed to predict postprandial metabolic responses. We identified individuals with IBS subtype according to the Rome III criteria based on predominant bowel habits during symptom onset: diarrhea (i.e. looser), constipation (i.e. harder), and mixed. Participants with IBS-D (n = 59) consumed more healthy plant-based foods (e.g. whole grains, leafy vegetables) and fiber, while those with IBS-C (n = 49) tended to consume more unhealthy plant-based foods (e.g. refined grains, fruit juice) than participants without IBS (n = 797). Microbial diversity was nominally lower in patients with IBS-D than in participants without IBS or with IBS-C. Using multivariable-adjusted linear regression, we identified specific microbiota variations in IBS subtypes, including slight increases in pro-inflammatory taxa in IBS-C (e.g. Escherichia coli) and loss of strict anaerobes in IBS-D (e.g. Faecalibacterium prausnitzii). Our analysis also revealed intriguing evidence of interactions between diet and Faecalibacterium prausnitzii. The positive associations between fiber and iron intake and IBS-diarrhea were stronger among individuals with a higher relative abundance of Faecalibacterium prausnitzii, potentially driven by carbohydrate metabolic pathways, including the superpathway of β-D-glucuronide and D-glucuronate degradation. In conclusion, our findings suggest subtype-specific variations in dietary habits, gut microbial composition and function, and diet-microbiota interactions in IBS, providing insights into potential microbiome-informed dietary interventions.
Opioid Use Disorder Treatment for Patients Who Are Incarcerated
Authors: Amelita Woodruff, Jordan Nahas-Vigon, Brian Yagi
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Population Characteristics and Organ Procurement Organization Performance Metrics
Authors: Rocio Lopez, Sumit Mohan, Jesse D. Schold
Journal: JAMA Network Open (2023)

In 2020, the Centers for Medicare & Medicaid Services (CMS) issued a final rule updating the Organ Procurement Organization (OPO) Conditions for Coverage. This rule evaluates OPO performance based on an unadjusted donation rate and an age-adjusted transplant rate; however, neither considers other underlying population differences.To evaluate whether adjusting for age and/or area deprivation index yields the same tier assignments as the cause, age, and location consistent (CALC) tier used by CMS.This retrospective cross-sectional study examined the performance of 58 OPOs from 2018 to 2020 across the entire US. A total of 12 041 778 death records were examined from the 2017 to 2020 National Center for Health Statistics' Restricted Vital Statistics Detailed Multiple Cause of Death files; 399 530 of these met the definition of potential deceased donor. Information about 42 572 solid organ donors from the Scientific Registry of Transplant Recipients was also used. Statistical analysis was performed from January 2017 to December 2020.Area deprivation of donation service areas and age of potential donors.OPO performance as measured by donation and transplant rates.A total of 399 530 potential deceased donors and 42 572 actual solid donor organs were assigned to 1 of 58 OPOs. Age and ADI adjustment resulted in 19.0% (11 of 58) to 31.0% (18 of 58) reclassification of tier ratings for the OPOs, with 46.6% of OPOs (27 of 58) changing tier ranking at least once during the 3-year period. Between 6.9% (4 of 58) and 12.1% (7 of 58) moved into tier 1 and up to 8.6% (5 of 58) moved into tier 3.This cross-sectional study of population characteristics and OPO performance metrics found that adjusting for area deprivation and age significantly changed OPO measured performance and tier classifications. These findings suggest that underlying population characteristics may alter processes of care and characterize donation and transplant rates independent of OPO performance. Risk adjustment accounting for population characteristics warrants consideration in prospective policy and further evaluation of quality metrics.
Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia
Authors: Jonathan D. Norton, Chan Zeng, Elizabeth A. Bayliss, Susan M. Shetterly, Nicole Williams, Emily Reeve, Matthew K. Wynia, Ariel R. Green, Melanie L. Drace, Kathy S. Gleason, Orla C. Sheehan, Cynthia M. Boyd
Journal: JAMA Network Open (2023)

Importance Physicians endorse deprescribing of risky or unnecessary medications for older adults (aged ≥65 years) with dementia, but there is a lack of information on what influences decisions to deprescribe in this population. Objective To understand how physicians make decisions to deprescribe for older adults with moderate dementia and ethical and pragmatic concerns influencing those decisions. Design, Setting, and Participants A cross-sectional national mailed survey study of a random sample of 3000 primary care physicians from the American Medical Association Physician Masterfile who care for older adults was conducted from January 15 to December 31, 2021. Main Outcomes and Measures The study randomized participants to consider 2 clinical scenarios in which a physician may decide to deprescribe a medication for older adults with moderate dementia: 1 in which the medication could cause an adverse drug event if continued and the other in which there is no evidence of benefit. Participants ranked 9 factors related to possible ethical and pragmatic concerns through best-worst scaling methods (from greatest barrier to smallest barrier to deprescribing). Conditional logit regression quantified the relative importance for each factor as a barrier to deprescribing. Results A total of 890 physicians (35.0%) returned surveys; 511 (57.4%) were male, and the mean (SD) years since graduation was 26.0 (11.7). Most physicians had a primary specialty in family practice (50.4% [449 of 890]) and internal medicine (43.5% [387 of 890]). A total of 689 surveys were sufficiently complete to analyze. In both clinical scenarios, the 2 greatest barriers to deprescribing were (1) the patient or family reporting symptomatic benefit from the medication (beneficence and autonomy) and (2) the medication having been prescribed by another physician (autonomy and nonmaleficence). The least influential factor was ease of paying for the medication (justice). Conclusions and Relevance Findings from this national survey study of primary care physicians suggests that understanding ethical aspects of physician decision-making can inform clinician education about medication management and deprescribing decisions for older adults with moderate dementia.
Early Metformin in Gestational Diabetes
Authors: Fidelma Dunne, Christine Newman, Alberto Alvarez-Iglesias, John Ferguson, Andrew Smyth, Marie Browne, Paula O’Shea, Declan Devane, Paddy Gillespie, Delia Bogdanet, Oratile Kgosidialwa, Aoife Egan, Yvonne Finn, Geraldine Gaffney, Aftab Khattak, Derek O’Keeffe, Aaron Liew, Martin O’Donnell
Journal: JAMA (2023)

Importance Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks’ postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, −6.9% [95% CI, −15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing &amp;amp;gt;4 kg, a lower proportion in the &amp;amp;gt;90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration ClinicalTrials.gov Identifier: NCT02980276 ; EudraCT: 2016-001644-19
Asymmetric Evolution of Protein Domains in the Leucine-Rich Repeat Receptor-Like Kinase Family of Plant Signaling Proteins
Authors: Jarrett Man, T A Harrington, Kyra Lally, Madelaine E Bartlett
Journal: Molecular Biology and Evolution (2023)

The coding sequences of developmental genes are expected to be deeply conserved, with cis-regulatory change driving the modulation of gene function. In contrast, proteins with roles in defense are expected to evolve rapidly, in molecular arms races with pathogens. However, some gene families include both developmental and defense genes. In these families, does the tempo and mode of evolution differ between genes with divergent functions, despite shared ancestry and structure? The leucine-rich repeat receptor-like kinase (LRR-RLKs) protein family includes members with roles in plant development and defense, thus providing an ideal system for answering this question. LRR-RLKs are receptors that traverse plasma membranes. LRR domains bind extracellular ligands; RLK domains initiate intracellular signaling cascades in response to ligand binding. In LRR-RLKs with roles in defense, LRR domains evolve faster than RLK domains. To determine whether this asymmetry extends to LRR-RLKs that function primarily in development, we assessed evolutionary rates and tested for selection acting on 11 subfamilies of LRR-RLKs, using deeply sampled protein trees. To assess functional evolution, we performed heterologous complementation assays in Arabidopsis thaliana (Arabidopsis). We found that the LRR domains of all tested LRR-RLK proteins evolved faster than their cognate RLK domains. All tested subfamilies of LRR-RLKs had strikingly similar patterns of molecular evolution, despite divergent functions. Heterologous transformation experiments revealed that multiple mechanisms likely contribute to the evolution of LRR-RLK function, including escape from adaptive conflict. Our results indicate specific and distinct evolutionary pressures acting on LRR versus RLK domains, despite diverse organismal roles for LRR-RLK proteins.
Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial
Authors: Armin Rashidi, Maryam Ebadi, Tauseef Ur Rehman, Heba Elhusseini, David Kazadi, Hossam Halaweish, Mohammad H. Khan, Andrea Hoeschen, Qing Cao, Xianghua Luo, Amanda J. Kabage, Sharon Lopez, Shernan G. Holtan, Daniel J. Weisdorf, Alexander Khoruts, Christopher Staley
Journal: Clinical Cancer Research (2023)

Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.
B cell–intrinsic <i>Myd88</i> regulates disease progression in murine lupus
Authors: Jeremy S. Tilstra, Minjung Kim, Rachael A. Gordon, Claire Leibler, Haylee A. Cosgrove, Sheldon Bastacky, Kevin M. Nickerson, Mark J. Shlomchik
Journal: The Journal of Experimental Medicine (2023)

Nucleic acid–specific Toll-like receptors (TLRs) have been implicated in promoting disease pathogenesis in systemic lupus erythematosus (SLE). Whether such TLRs mediate disease onset, progression, or both remains undefined; yet the answer to this question has important therapeutic implications. MyD88 is an essential adaptor that acts downstream of IL-1 family receptors and most TLRs. Both global and B cell–specific Myd88 deficiency ameliorated disease in lupus-prone mice when constitutively deleted. To address whether Myd88 was needed to sustain ongoing disease, we induced B cell–specific deletion of Myd88 after disease onset in MRL.Faslpr mice using an inducible Cre recombinase. B cell–specific deletion of Myd88 starting after disease onset resulted in ameliorated glomerulonephritis and interstitial inflammation. Additionally, treated mice had reduced autoantibody formation and an altered B cell compartment with reduced ABC and plasmablast numbers. These experiments demonstrate the role of MyD88 in B cells to sustain disease in murine lupus. Therefore, targeting MyD88 or its upstream activators may be a viable therapeutic option in SLE.